Kane, Sunanda V.

Abstract Approximately 50% of patients with inflammatory bowel disease including both Crohn’s disease and ulcerative colitis are female with many being diagnosed and treated during their reproductive years. It is important for women to be in remission prior to and during pregnancy. There have been many advances in the treatment of inflammatory bowel disease, including new therapies. In this review, we summarize the currently approved medications for Crohn’s disease and their safety in pregnancy and postpartum. The totality of evidence suggests that the majority of therapies are low-risk before and during pregnancy, and should be continued to control maternal disease.

INTRODUCTION: We evaluated the real-world effectiveness and safety of ustekinumab (UST) in patients with Crohn's disease (CD). METHODS: This study used a retrospective, multicenter, multinational consortium of UST-treated CD patients. Data included patient demographics, disease phenotype, disease activity, treatment history, and concomitant medications. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions were assessed using time-to-event analysis, and clinical predictors were assessed by using multivariate Cox proportional hazard analyses. Serious infections and adverse events were defined as those requiring hospitalization or treatment discontinuation. RESULTS: A total of 1,113 patients (51.8% female, 90% prior antitumor necrosis factor exposure) were included, with a median follow-up of 386 days. Cumulative rates of clinical, steroid-free, endoscopic, and radiographic remissions at 12 months were 40%, 32%, 39%, and 30%, respectively. Biologic-naive patients achieved significantly higher rates of clinical and endoscopic remissions at 63% and 55%, respectively. On multivariable analyses, prior antitumor necrosis factor (hazard ratio, 0.72; 95% confidence interval, 0.49–0.99) and vedolizumab exposure (hazard ratio, 0.65; 95% confidence interval, 0.48–0.88) were independently associated with lower likelihoods of achieving endoscopic remission. In patients who experienced loss of remission, 77 of 102 (75%) underwent dose optimization, and 44 of 77 (57%) achieved clinical response. An additional 152 of 681 patients (22.3%) were dose-optimized because of primary nonresponse incomplete response to UST, of whom 40.1% (61 of 152) responded. Serious infections occurred in 3.4% of patients while other noninfectious adverse events (lymphoma [n = 1], arthralgia [n = 6], rash [n = 6], headache [n = 3], hepatitis [n = 3], hair loss [n = 3], neuropathy [n = 1], and vasculitis [n = 1]) occurred in 2.4% of patients. DISCUSSION: UST represents a safe and effective treatment option for CD, with 40% of patients from a highly refractory cohort achieving clinical remission by 12 months. The greatest treatment effect of UST was seen in biologic-naive patients, and dose escalation may recapture clinical response.

LINKED CONTENTThis article is linked to Friedman et al papers. To view these articles, visit https://doi.org/10.1111/apt.17113

Abstract Background Menopause, defined by the complete cessation of menstrual cycles for 12 consecutive months, may occur at a younger age in women who have concomitant immune dysregulation. Our aim was to determine whether women with inflammatory bowel disease (IBD) experience an earlier onset of menopause compared to women without IBD. Methods This was a retrospective cohort study using resources of the Rochester Epidemiology Project, a collaboration between clinics, hospitals, and medical facilities in Olmsted County, Minnesota. From these people, women who were diagnosed with IBD between 1970 and 2010 comprised the case cohort while the reference cohort included women with no diagnosis of IBD. Data including age, body mass index (BMI), ethnicity, smoking status, age at onset of menopause, and current use of hormone therapy were collected. Patients with history of hysterectomy or oophorectomy were excluded. Wilcoxon rank-sum test for numeric variables and Fisher’s exact test for categorical variables were used to analyze the data. Results A total of 171 women met criteria for inclusion (83 cases and 88 controls). Mean age of menopause in women with IBD was 50.0 years compared to 51.5 years in women with no IBD (P = .006). There was no difference in BMI of women with and without IBD (28.7 versus 28.2 kg m−2; P = .9), respectively. There were more former smokers (33.7%) and current (6%) smokers in the IBD group (P = .009) compared to the non-IBD group. Conclusions IBD is associated with an earlier onset of menopause. Although it is unclear if this mean difference of 1.5 years is clinically relevant, it is known that early menopause is associated with an increased risk of osteoporosis and cardiovascular disease. Further research on the possible mechanisms is needed.

Abstract When the only biologics were antitumor necrosis factor agents, it was not hard to treat our sick Crohn's patients. Now with multiple mechanisms of action, the therapeutic landscape is more broad but can be confusing. Trying to compare agents is difficult because head-to-head trials are lacking. A comparative effectiveness methodology allows for indirect comparisons of agents based on the outcome of interest. When deciding what agent is “best” for any specific patient, multiple factors have to be taken into consideration including the primary outcome of interest. In this study, the outcome of mucosal healing is considered.

Abstract Background Microscopic colitis (MC) is suspected to result from increased immune activity in gut mucosa. Immune checkpoint inhibitors (ICIs) treat cancer by activating the immune system, and further investigation is needed regarding their role in the development of MC. Methods A retrospective case series investigated cases of endoscopically and histologically confirmed MC developing after administration of ICIs. Clinical notes and medication administration records were reviewed for demographics, symptom duration, and treatment response. Results Nineteen cases of de novo MC were identified, with 95% of cases requiring steroid treatment, 53% presenting with hospitalization, and colitis-related mortality in 1 individual. Symptom onset occurred a median of 160 days after initiation of ICI therapy and 53 days after their most recent dose of therapy. Patients had a median of 125 days of symptoms, and ICI therapy was held in 70% of individuals due for treatment. Conclusions MC can develop after ICI administration, and presents with severe symptoms, often requiring hospitalization and steroid treatment. In certain individuals this can require a prolonged treatment course of steroid therapy or immunomodulators. Individuals developing diarrhea after ICI therapy warrant thorough workup including endoscopy and rapid treatment initiation given the disease severity observed in this series.

ABSTRACT Fibrodysplasia ossificans progressiva (FOP) is a rare disease characterized by inflammatory flares of soft tissues, leading to heterotopic ossification and significant cumulative morbidity and early mortality. FOP minor trauma, including intramuscular medication administration, can induce ossification and should be avoided. We present a case of known FOP in a patient who presented with fevers of unknown origin and was found to have biopsy-proven ileal Crohn's disease. Crohn's disease management was complicated by concerns that intramuscular therapies would induce ossification, and oral monotherapy with methotrexate was initiated with excellent results.

Abstract Background Oral contraceptive pill (OCP) use in the general population is associated with a failure rate as low as 0.3% with perfect use but as high as 9% with typical use. Women with Crohn’s disease (CD) may have malabsorption in the setting of small bowel disease or resection, which could affect absorption of OCPs. Our aim was to determine the incidence of pregnancy in women with CD on OCPs. Methods This is a retrospective study assessing the incidence rate of OCP failure in females between 18 and 45 years of age seen at the Mayo Clinic with a diagnosis of CD and provided a prescription for OCPs, between 2016 and 2020. Failure was defined as clear documentation of becoming pregnant while using OCPs or having an active prescription of OCP at the time of conception. Results A total of 818 female patients with CD between 18 and 45 years of age with a prescription for an OCP were included in our study. Sixty-six patients (8%) conceived in this cohort. Of the 66 patients who became pregnant, 57 stopped the OCP before conceiving, 5 were excluded due to lack of data, and 4 women had active oral contraceptive prescriptions when they became pregnant (pregnancy rate of 0.5%). Conclusions In female patients with CD who are using OCPs for contraception, we found a low rate of pregnancy (0.5%) similar to the rate of pregnancy with perfect use of OCPs in the general population. OCPs are an effective method of birth control in women with CD.